The overall objective of this research project is to understand the basic mechanisms of epileptogenesis in a variety of experimental models of epilepsy using light and electron microscopic immunocytochemical methods. The specific aims of this proposal include further studies of the system as well as an analysis of the neural-specific, cyclic AMP-dependent protein kinase The planned experiments will involve the genetically epilepsy-prone rat (GEPR), and the gel treated monkey. The specific aims related to the GEPR include: 1) a quantitative of the GABAergic neurons and total number of small neurons in the inferior colliculus (IC) of the moderately-seizing strain of GEPR, the GEPR-3; 2) Light and electron microscopic immunocytochemical studies of the IC will be made to determine whether an alteration in the distribution of GABA receptors occurs in GEPRS; 3) Light and electron rrucroscopic immunocytochemical studies with antibodies to the regulatory (RII-B) subunits of the neuralspecific, cyclic AMP-dependent protein kinase will be used to determine whether cyclic AMP receptors are increased in the IC of GEPRS; 4) an analysis will be made of RII-B immunoreactivity age-matched offspring from GEPR-9s, GEPR-3s and SD rats to determine whether an increase in RII-B immunoreactivity occurs prior to the development of seizure activity; 5) Co-localization studies will be made at the electron microscopic level using the same antibodies described in 2 & 3 determine whether GABA-A receptors are found associated with the same postsynaptic densities that display RII-B immunoreactivity; 6) Sections with RII-B localized to postsynaptic densities will be incubated with antibodies to glutamate decarboxylase, glutamate or dopamine B-hydroxylase to localize axon terminals containing GABA, glutamate or norepinephrine, respectively, to determine whether RII-B is associated with specific types of synapses. The previous studies of alumina gel treated monkeys involved injections into the hand region of the sensorimotor cortex where cortical ABAergic neurons were selectively destroyed prior to the onset of seizure activity. To determine how alumina gel injections into the temporal lobe cause epilepsy in monkeys, a number of monkeys with such injections will be analyzed for GABAergic neurons and terminals using immunocytochemical methods. Together, these studies will provide new information about the basic mechanisms of epilepsy.